Management and Outcomes of Patients at a Specialty Clinic for Clostridioides difficile Infection.

Vancomycin and fidaxomicin taper regimens were the most common treatment strategies employed but nearly half of patients (40/83) referred to our Clostridioides difficile infection (CDI) clinic did not require further treatment. The overall 60-day CDI recurrence rate was 16.9% (11/65). CDI management at a dedicated clinic may improve clinical outcomes.

Navigating Multiple Challenges: Malnutrition and Nephrotoxic Drug Effects in a Non-verbal Child With Autism Spectrum Disorder Requiring Dialysis.

Acute kidney injury (AKI) is a common medication adverse event, particularly in patients with pre-existing medical conditions taking nephrotoxic medications. However, little is known about the differences in the risk of nephrotoxic medication-related complications in children with autism spectrum disorder (ASD) compared to the general pediatric population. A nine-year-old non-verbal boy with ASD was hospitalized for scrotal cellulitis requiring vancomycin and piperacillin/tazobactam due to a lack of clinical response to cephalosporins. His history is significant for being an extremely selective eater, and his appetite decreased over four months prior to presentation. Poorly controlled scrotal pain, despite acetaminophen use, was suspected based on his facial expressions and maternal assessment, especially considering his non-verbal status. Consequently, a non-steroidal anti-inflammatory drug was initiated. The hospital course was complicated by the development of a scrotal abscess, minimal enteral intake, hypoalbuminemia-induced intravascular dehydration, oliguria, and generalized edema. His creatinine increased to 5.11 mg/dL from 0.51 mg/dL despite early discontinuation of nephrotoxic medications and fluid resuscitation, which led to hemodialysis due to worsening AKI. Subsequently, urinary output and edema improved. Creatinine improved to <1 mg/dL with careful creatinine monitoring and concomitant furosemide and albumin infusion in the pediatric intensive care unit. Children with comorbidities, such as malnutrition, who require nephrotoxic medications, need extra attention. Implementing clinical decision support tools or quality improvement programs can promote the prevention of nephrotoxic medication exposure and decrease the incidence of AKI. An alert within an electronic health record system for multiple nephrotoxic drugs and daily multidisciplinary huddles during patient-centered rounds could help reduce and eliminate adverse events. In particular, for non-verbal patients or those with limited communication skills, such as children with ASD, rigorous and close monitoring of vital signs, physical condition, pain, medication intake, and lab results, in addition to a nephrotoxic medication screening and notification system, should be key to optimizing patient care.

Local vancomycin administration in Orthopaedic Surgery - A systematic review of comparative studies.

Background: There is still controversy surrounding the routine use of vancomycin locally in primary orthopaedic surgery procedures. Therefore, the aim of this review is to assess how local vancomycin impacts the rates and microbiology of surgical site infections. Methods: A systematic electronic search of MEDLINE, EMBASE, and Web of Science was carried out for all comparative studies comparing locally applied vancomycin to control for primary orthopaedic surgery procedures published before August 14, 2022. Results: A total of 61 studies with 65,671 patients were included for analysis. Forty-six studies used vancomycin powder, 12 studies with grafts soaked in vancomycin, two studies used vancomycin irrigation, and one study administered vancomycin interosseously. There were 15 studies (of 26) in spine surgery, five (of 14) in arthroplasty, ten (of 11) in sports medicine, and two (of five) in trauma surgery that found statistically significant decreases in overall infection rates when applying local vancomycin. Only one study (in spine surgery) found significant increases in infection rates with local vancomycin application. For spine surgery, local vancomycin application had the greatest proportion of gram-negative bacteria (40.7%) isolated compared to S. aureus (42.4%) in controls. In arthroplasty and trauma surgery, there were increases in the proportions of gram-negative bacteria when vancomycin was added. There were no reported systemic adverse reactions associated with local vancomycin use in any of the studies. Conclusion: Applying local vancomycin during primary orthopaedic surgery procedures may reduce the rates of infections in multiple different orthopaedic specialties, particularly in spine surgery and sports medicine. However, careful consideration should be applied when administering local vancomycin during specific orthopaedic procedures given the heterogeneity of included studies and breadth of surgeries included in this review. Level of evidence: Level III. A systematic review of level I - III studies.

Detection of Vancomycin Resistance among Methicillin-Resistant Staphylococcus aureus Strains Recovered from Children with Invasive Diseases in a Reference Pediatric Hospital.

Vancomycin is the cornerstone in treating methicillin-resistant Staphylococcus aureus (MRSA) infections. However, therapeutic failures can occur when MRSA strains with decreased susceptibility to glycopeptides (DSG) are involved. The aim of this study was to detect and characterize DSG in MRSA recovered from children with invasive diseases at a reference pediatric hospital between 2009 and 2019. Fifty-two MRSA strains were screened using agar plates with vancomycin 3 and 4 mg/L (BHI-3 and BHI-4); the VITEK2 system; and standard and macro E-tests. Suspicious hVISA were studied by population analysis profiling-area under the curve (PAP-AUC), and wall thickness was analyzed by transmission electron microscopy. Neither VRSA nor VISA were detected in this set. As only three strains met the hVISA criteria, the PAP-AUC study included 12 additional MRSA strains that grew one colony on BHI-4 plates or showed minimum inhibitory concentrations of vancomycin and/or teicoplanin ≥ 1.5 mg/L. One strain was confirmed as hVISA by PAP-AUC. The wall thickness was greater than the vancomycin-susceptible control strain; it belonged to ST30 and carried SCCmec IV. As expected, a low frequency of hVISA was found (1.9%). The only hVISA confirmed by PAP-AUC was not detected by the screening methods, highlighting the challenge that its detection represents for microbiology laboratories.

Age-Related Differences in Vancomycin-Associated Nephrotoxicity and Efficacy in Methicillin-Resistant Staphylococcus aureus Infection: A Comparative Study between Elderly and Adult Patients.

Elderly patients (age ≥ 65 years) are susceptible to methicillin-resistant Staphylococcus aureus (MRSA) infections, with potential for more adverse treatment outcomes or complications compared to younger adults (18-64 years). This study compared vancomycin-associated nephrotoxicity and efficacy in elderly and adult patients and investigated the correlation between vancomycin pharmacokinetic/pharmacodynamic (PK/PD) indices and clinical outcomes. A prospective study was conducted in 10 hospitals in Shanghai from October 2012 to November 2019. A total of 164 patients with MRSA infections were enrolled, including 83 elderly and 81 adult patients. Vancomycin therapeutic drug monitoring (TDM) was performed in all patients, indicating significantly higher vancomycin trough concentrations (Ctrough), 24-h area under the curve (AUC24) values, and AUC24/minimum inhibitory concentration (AUC24/MIC) values in elderly patients compared to adult patients. The incidence of vancomycin-associated nephrotoxicity was nearly three times higher in elderly patients (18.1% vs. 6.2%, p = 0.020), despite similar clinical and microbiological efficacy. Of particular importance, a Ctrough > 20 mg/L was found as an independent factor of nephrotoxicity in elderly patients. Further analysis of patients with an estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2 also revealed that elderly patients had significantly higher vancomycin-related PK/PD indices and more nephrotoxicity than adult patients. In conclusion, elderly patients receiving vancomycin therapy face a higher risk of nephrotoxicity, which requires close vancomycin TDM, especially when the Ctrough exceeds 20 mg/L.

Efficacy Assessment of the Co-Administration of Vancomycin and Metronidazole in Clostridioides difficile-Infected Mice Based on Changes in Intestinal Ecology.

Vancomycin (VAN) and metronidazole (MTR) remain the current drugs of choice for the treatment of non-severe Clostridioides difficile infection (CDI); however, while their co-administration has appeared in clinical treatment, the efficacy varies greatly and the mechanism is unknown. In this study, a CDI mouse model was constructed to evaluate the therapeutic effects of VAN and MTR alone or in combination. For a perspective on the intestinal ecology, 16S rRNA amplicon sequencing and non-targeted metabolomics techniques were used to investigate changes in the fecal microbiota and metabolome of mice under the co-administration treatment. As a result, the survival rate of mice under co-administration was not dramatically different compared to that of single antibiotics, and the former caused intestinal tissue hyperplasia and edema. Co-administration also significantly enhanced the activity of amino acid metabolic pathways represented by phenylalanine, arginine, proline, and histidine, decreased the level of deoxycholic acid (DCA), and downregulated the abundance of beneficial microbes, such as Bifidobacterium and Akkermansia. VAN plays a dominant role in microbiota regulation in co-administration. In addition, co-administration reduced or increased the relative abundance of antibiotic-sensitive bacteria, including beneficial and harmful microbes, without a difference. Taken together, there are some risks associated with the co-administration of VAN and MTR, and this combination mode should be used with caution in CDI treatment.

Association of Vancomycin AUC/MIC and Trough Concentration With Early Clinical Response in Enterococcus or Coagulase-Negative Staphylococcus Infection: A Prospective Study.

This study was condcuted to examine the association of area under the curve (AUC)/minimum inhibitory concentration (MIC) and trough concentration (Ctrough) of vancomycin with treatment outcome and nephrotoxicity in infections caused by Enterococcus spp. and coagulase-negative Staphylococci (CoNS). Peak and trough concentrations were used to calculate AUC in 89 patients receiving vancomycin for infections with Enterococcus spp. (n = 65) or CoNS (n = 24). Correlations between Ctrough, AUC/MIC, early clinical response (ECR), and nephrotoxicity were assessed and cutoff values were determined. Sixty-three (70.8%) patients showed improvement in ECR and 10 (11.2%) experienced nephrotoxicity. Enterococcus spp. infections displayed correlations between AUC/MIC and ECR for AUC0-24 h/MIC (r2 = 0.27, P ≤ .05) and AUC24-48 h/MIC (r2 = 0.28, P ≤ .05), but not for Ctrough (r2 = 0.21, P > .05). There were no correlations between Ctrough (r2 = 0.26, P > .05), AUC0-24 h/MIC (r2 = -0.12, P > .05), AUC24-48 h/MIC (r2 = 0.01, P > .05) and ECR for CoNS. In the CoNS group, a moderate correlation was found between ECR and Ctrough at a cutoff value of 6.9 µg/mL. In addition, nephrotoxicity is also moderately associated with AUC0-24 h and AUC24-48 h at 505.7 and 667.1 µg•h/mL, respectively. A strong correlation between nephrotoxicity and Ctrough was observed when the cutoff value was 18.9 µg/mL. AUC/MIC during the first 48 h was a determinant of vancomycin efficacy in Enterococcus infections but not for CoNS. Ctrough was not correlated with clinical outcome. Nephrotoxicity could be predicted using Ctrough and AUC for infections with both pathogens.

Synthesis and preclinical evaluation of novel 18F-vancomycin-based tracers for the detection of bacterial infections using positron emission tomography.

INTRODUCTION: Bacterial infections are a major problem in medicine, and the rapid and accurate detection of such infections is essential for optimal patient outcome. Bacterial infections can be diagnosed by nuclear imaging, but most currently available modalities are unable to discriminate infection from sterile inflammation. Bacteria-targeted positron emission tomography (PET) tracers have the potential to overcome this hurdle. In the present study, we compared three 18F-labelled PET tracers based on the clinically applied antibiotic vancomycin for targeted imaging of Gram-positive bacteria. METHODS: [18F]FB-NHS and [18F]BODIPY-FL-NHS were conjugated to vancomycin. The resulting conjugates, together with our previously developed [18F]PQ-VE1-vancomycin, were tested for stability, lipophilicity, selective binding to Gram-positive bacteria, antimicrobial activity and biodistribution. For the first time, the pharmacokinetic properties of all three tracers were compared in healthy animals to identify potential binding sites. RESULTS: [18F]FB-vancomycin, [18F]BODIPY-FL-vancomycin, and [18F]PQ-VE1-vancomycin were successfully synthesized with radiochemical yields of 11.7%, 2.6%, and 0.8%, respectively. [18F]FB-vancomycin exhibited poor in vitro and in vivo stability and, accordingly, no bacterial binding. In contrast, [18F]BODIPY-FL-vancomycin and [18F]PQ-VE1-vancomycin showed strong and specific binding to Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), which was outcompeted by unlabeled vancomycin only at concentrations exceeding clinically relevant vancomycin blood levels. Biodistribution showed renal clearance of [18F]PQ-VE1-vancomycin and [18F]BODIPY-FL-vancomycin with low non-specific accumulation in muscles, fat and bones. CONCLUSION: Here we present the synthesis and first evaluation of the vancomycin-based PET tracers [18F]BODIPY-FL-vancomycin and [18F]PQ-VE1-vancomycin for image-guided detection of Gram-positive bacteria. Our study paves the way towards real-time bacteria-targeted diagnosis of soft tissue and implant-associated infections that are oftentimes caused by Gram-positive bacteria, even after prophylactic treatment with vancomycin.

Application of machine learning combined with population pharmacokinetics to improve individual prediction of vancomycin clearance in simulated adult patients.

Background and aim: Vancomycin, a glycopeptide antimicrobial drug. PPK has problems such as difficulty in accurately reflecting inter-individual differences, and the PPK model may not be accurate enough to predict individual pharmacokinetic parameters. Therefore, the aim of this study is to investigate whether the application of machine learning combined with the PPK method can improve the prediction of vancomycin CL in adult Chinese patients. Methods: In the first step, a vancomycin CL prediction model for Chinese adult patients is given by PPK and Hamilton Monte Carlo sampling is used to obtain the reference CL of 1,000 patients; the second step is to obtain the final prediction model by machine learning using an appropriate model for the predictive factor and the reference CL; and the third step is to randomly select, in the simulated data, a total of 250 patients for prediction effect evaluation. Results: XGBoost model is selected as final machine learning model. More than four-fifths of the subjects' predictive values regarding vancomycin CL are improved by machine learning combined with PPK. Machine learning combined with PPK models is more stable in performance than the PPK method alone for predicting models. Conclusion: The first combination of PPK and machine learning for predictive modeling of vancomycin clearance in adult patients. It provides a reference for clinical pharmacists or clinicians to optimize the initial dosage given to ensure the effectiveness and safety of drug therapy for each patient.

A case report of Vancomycin in the treatment of Q fever endocarditis.

The patient, a 43-year-old male, was admitted to the hospital with gradually aggravated exertional palpitations and chest tightness over a 2-day period. Upon hospital admission, a cardiac ultrasound revealed aortic valve redundancy, however multiple blood culture investigations came back negative. Blood mNGS was perfected, revealing Coxiella burnetii, and the diagnosis of Q fever (query fever) was established. The temperature and inflammatory indices of the patient were all normal with the treatment of vancomycin before cardiac surgery. But for the potential liver damage of and the Coxiella burnetii was still positive in the anti-phase II IgG titer, the doxycycline and hydroxychloroquine instead of vancomycin were applied for the patient. Despite receiving standardized anti-infective therapy of doxycycline combined with hydroxychloroquine, this patient had fever and increased leukocytes following surgery. After the addition of vancomycin as an anti-infective treatment, the temperature and leukocytes improved quickly. During the treatment of vancomycin, a discovery of liver injury may have resulted. These findings provide new therapy options for future professionals.

Prospective validation of a model-informed precision dosing tool for vancomycin treatment in neonates.

We recruited 48 neonates (50 vancomycin treatment episodes) in a prospective study to validate a model-informed precision dosing (MIPD) software. The initial vancomycin dose was based on a population pharmacokinetic model and adjusted every 36-48 h. Compared with a historical control group of 53 neonates (65 episodes), the achievement of a target trough concentration of 10-15 mg/L improved from 37% in the study to 62% in the MIPD group (P = 0.01), with no difference in side effects.

Intraosseous Regional Administration of Vancomycin Prophylaxis for Primary and Revision Total Knee Arthroplasty.

The advantages of prophylaxis with intraosseous regional administration (IORA) of vancomycin for periprosthetic joint infection (PJI) in primary and revision total knee arthroplasty (TKA) include the ability to deliver antibiotics directly to the surgical bed and avert systemic delivery; the ability to precisely time and quickly administer vancomycin to achieve the highest concentrations at the beginning and throughout the surgical procedure; and the ability to avert several common and potentially serious adverse effects of intravenous vancomycin. Indications for IORA of vancomycin prophylaxis include the following clinical scenarios: revision TKA; obesity; diabetes; beta-lactam allergy; known colonization with methicillin-resistant Staphylococcus aureus (MRSA); individuals coming from institutions with a high MRSA incidence; previous ligamentous surgical procedure or osteotomy; current or recent smokers; in the primary TKA setting if the individual is considered high-risk as defined by the criteria above; and during reimplantation following 2-stage exchange for PJI.

Staphylococcus aureus nasal colonization and susceptibility profile to antimicrobials in hemodialysis patients using a protocol of seven collections.

BACKGROUND: Patients colonized with Staphylococcus aureus in their nasal passages have a higher risk of acquiring infection, especially if they are immunocompromised or have comorbidities such as chronic renal failure undergoing hemodialysis (HD). OBJECTIVE: This study aimed to report the prevalence of nasal carriage of S. aureus among HD patients utilizing a seven-week sampling protocol and to assess the susceptibility of these isolates to various antimicrobial agents. METHODS: Over seven consecutive weeks, nasal swab samples were collected from 47 HD patients, resulting in a total of 329 samples. The microorganisms were identified using biochemical methods and subjected to antimicrobial susceptibility testing via disk diffusion and microdilution techniques. RESULTS: Out of all the patients analyzed, 25 individuals (53.19%) were found to be colonized by S. aureus, with 21 of them displaying intermittent colonization. Additionally, 38% showed positive results for S. aureus in only the 6th or 7th week of sampling. Within the 58 isolates, 17.2% (n=10) exhibited methicillin (oxacillin)-resistance and 25.86% (n=15) displayed elevated vancomycin MIC values (2 µg/ml). Based on the results, daptomycin and gentamicin were found to be effective treatment options. However, 31% of the isolates (n=18) exhibited a MIC of 1 µg/ml for daptomycin. CONCLUSION: Over half of the patients were colonized by S. aureus, but mostly on an intermittent basis. The identification of oxacillin resistance and high vancomycin and daptomycin MICs serve as warnings for possible future complications in managing bacteremia caused by S. aureus in these patients.

Early Initiation of Ceftaroline-Based Combination Therapy for Methicillin-resistant Staphylococcus aureus Bacteremia.

Purpose: Monotherapy with vancomycin or daptomycin remains guideline-based care for methicillin-resistant Staphylococcus aureus bacteremia (MRSA-B) despite concerns regarding efficacy. Limited data support potential benefit of combination therapy with ceftaroline as initial therapy. We present an assessment of outcomes of patients initiated on early combination therapy for MRSA-B. Methods: This was a single-center, retrospective study of adult patients admitted with MRSA-B between July 1, 2017 and April 31, 2023. During this period, there was a change in institutional practice from routine administration of monotherapy to initial combination therapy for most patients with MRSA-B. Combination therapy included vancomycin or daptomycin plus ceftaroline within 72 hours of index blood culture and monotherapy was vancomycin or daptomycin alone. The primary outcome was a composite of persistent bacteremia, 30-day all-cause mortality, and 30-day bacteremia recurrence. Time to microbiological cure and safety outcomes were assessed. All outcomes were assessed using propensity score-weighted logistic regression. Results: Of 213 patients included, 118 received monotherapy (115 vancomycin, 3 daptomycin) and 95 received combination therapy with ceftaroline (76 vancomycin, 19 daptomycin). The mean time from MRSA-positive molecular diagnostic blood culture result to combination therapy was 12.1 hours. There was no difference between groups for the primary composite outcome (OR 1.58, 95% CI 0.60, 4.18). Time to microbiological cure was longer with combination therapy (mean difference 1.50 days, 95% CI 0.60, 2.41). Adverse event rates were similar in both groups. Conclusions: Early initiation of ceftaroline-based combination therapy did not improve outcomes for patients with MRSA-B in comparison to monotherapy therapy.

Analysis of Vancomycin Dosage and Plasma Levels in Critically Ill Adult Patients Requiring Extracorporeal Membrane Oxygenation (ECMO).

Introduction: Critically ill patients undergoing extracorporeal membrane oxygenation (ECMO) exhibit unique pharmacokinetics. This study aimed to assess the achievement of vancomycin therapeutic targets in these patients. Methods: This retrospective cohort study included patients on ECMO treated with vancomycin between January 2010 and December 2018. Ninety patients were analyzed based on ECMO connection modality, baseline creatinine levels, estimated glomerular filtration rate (eGFR), renal replacement therapy (RRT) requirements, and vancomycin loading dose administration. Results: Twenty-three percent of the patients achieved the therapeutic range defined by baseline levels. No significant differences in meeting the therapeutic goal were found in multivariate analysis considering ECMO cannulation modality, initial creatinine level, initial eGFR, RRT requirement, or loading dose use. All trough levels between 15 and 20 mcg/mL achieved an estimated area under the curve/minimum inhibitory concentration (AUC/MIC) between 400 and 600, almost all trough levels over 10 mcg/mL predicted an AUC/MIC >400. Discussion: Achieving therapeutic plasma levels in these patients remains challenging, potentially due to factors such as individual pharmacokinetics and pathophysiology. A trough plasma level between 12 and 20 estimated the therapeutic AUC/MIC for all models, proposing a possible lower target, maintaining exposure, and potentially avoiding adverse effects. Despite being one of the largest cohorts of vancomycin use in ECMO patients studied, its retrospective nature and single-center focus limits its broad applicability.

Status of vancomycin-resistant Enterococcus in species of wild birds: A systematic review and meta-analysis.

Wild birds could be a reservoir of medically relevant microorganisms, particularly multidrug-resistant Enterococcus spp. Resistant bacteria's epidemiology and transmission between animals and humans has grown, and their zoonotic potential cannot be ignored. This is the first study to evaluate the status of vancomycin resistant enterococci (VRE) in various wild bird species using meta-analysis and a systematic review. In this study, the pooled prevalence was obtained by analyzing data from published articles on the occurrence of VRE in wild bird species. It's unclear how the antibiotic resistance gene transfer cycle affects wild birds. Google Scholar and PubMed were used to conduct the research. The data and study methodology was assessed and extracted by two reviewers independently, with a third reviewing the results. Heterogeneity between study and publication bias were analyzed using the random effect model. Thirty-eight studies were included in the meta-analysis. 382 out of the 4144 isolates tested, were VRE. The pooled prevalence of VRE among wild birds was estimated at 11.0% (95% CI; 6.9 -17.2%; I2 = 93.204%; P < 0.001). There was high variability between study (t2 = 2.156; heterogeneity I2 = 93.204% with chi-square (Q) = 544.413, degrees of freedom (df) = 37, and P < 0.001). Egger's test verified the funnel plot's bias, while result from the leave-one-out forest plot had no effect on the pooled prevalence.

Effects of sub-inhibitory concentrations of nafcillin, vancomycibipn, ciprofloxacin, and rifampin on biofilm formation of clinical methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) infections are often difficult to treat because of their biofilm-forming ability and antimicrobial resistance. We investigated the effects of sub-minimal inhibitory concentrations (MICs) of antibiotics on MRSA biofilm formation. Clinical MRSA isolates were grown with sub-MICs (1/256-1/2 × MICs) of nafcillin, vancomycin, ciprofloxacin, and rifampin. The biofilm biomass was measured using crystal violet staining. Of the 107 MRSA isolates tested, 63 (58.9%) belonged to sequence type 5 (ST5), and 44 (41.1%) belonged to ST72. The MIC50/MIC90 values of nafcillin, vancomycin, ciprofloxacin, and rifampin were 256/512, 1/2, 64/512, and 0.008/0.03 mg/L, respectively. The sub-MICs of nafcillin, vancomycin, ciprofloxacin, and rifampin promoted biofilm formation in 75 (70.1%), 49 (45.8%), 89 (83.2%), and 89 (83.2%) isolates, respectively. At sub-MICs of nafcillin, the factors associated with strong biofilm induction were the ST5 strain (P = 0.001) and agr dysfunction (P = 0.005). For the sub-MICs of ciprofloxacin, the associated factors were the ST5 strain (P = 0.002), staphylococcal protein A type t002 strain (P < 0.001), and ciprofloxacin resistance (P < 0.001). Among the sub-MICs of rifampin, only ST5 was associated with strong biofilm induction (P = 0.006). Because the sub-MICs of rifampin were much lower than clinically relevant concentrations, we further tested the capability of biofilm induction in 0.03[Formula: see text]32 mg/L of rifampin. At these concentrations, rifampin-induced biofilm formation was rare in rifampin-susceptible MRSA [1.0% (1 of 100)] but common in rifampin-resistant MRSA [71.4% (5 of 7), P < 0.001]. Induction of biofilm biomass at sub-MICs of antibiotics is common in clinical MRSA isolates and is differentially affected by the MRSA strain and antibiotic class. IMPORTANCE: Bacteria can be exposed to sub-MICs of antibiotics at the beginning and end of a dosing regimen, between doses, or during low-dose therapies. Growing evidence suggests that sub-MICs of antimicrobials can stimulate MRSA biofilm formation and alter the composition of the biofilm matrix. Pevious studies have found that sub-MICs of oxacillin, methicillin, and amoxicillin promote biofilm formation in some community-acquired MRSA (CA-MRSA). We evaluated biofilm induction by sub-MICs of four different classes of antibiotics in 44 CA-MRSA and 63 healthcare-associated MRSA (HA-MRSA) strains. Our study indicated that sub-MICs of nafcillin, vancomycin, ciprofloxacin, and rifampin frequently promote biofilm induction in clinical MRSA isolates. Strong biofilm induction in sub-MICs of nafcillin, ciprofloxacin, and rifampin was more frequent in HA-MRSA than in CA-MRSA. Antibiotic-induced biofilm formation depends on the antibiotic class, MRSA strain, and antibiotic resistance. Our results emphasize the importance of maintaining effective bactericidal concentrations of antibiotics to treat biofilm-related infections.

A Far-Red Fluorescent Probe to Visualize Gram-Positive Bacteria in Patient Samples.

Gram-positive bacteria, in particular Staphylococcus aureus (S. aureus), are the leading bacterial cause of death in high-income countries and can cause invasive infections at various body sites. These infections are associated with prolonged hospital stays, a large economic burden, considerable treatment failure, and high mortality rates. So far, there is only limited knowledge about the specific locations where S. aureus resides in the human body during various infections. Hence, the visualization of S. aureus holds significant importance in microbiological research. Herein, we report the development and validation of a far-red fluorescent probe to detect Gram-positive bacteria, with a focus on staphylococci, in human biopsies from deep-seated infections. This probe displays strong fluorescence and low background in human tissues, outperforming current tools for S. aureus detection. Several applications are demonstrated, including fixed- and live-cell imaging, flow cytometry, and super-resolution bacterial imaging.

Wide use of broad-spectrum antibiotics in very low birth weight infants with spontaneous focal intestinal perforation-is it really justified?

PURPOSE: Very low birth weight (VLBW) infants are at a risk of spontaneous focal intestinal perforation (FIP). Treatment includes supportive care, antibiotics, and drainage with/without surgery. Broad-spectrum antibiotic agents like carbapenems are applied frequently, although their use is not well-supported by the limited evidence of causal pathogens. We hypothesize that the use of carbapenems may not be necessary in VLBW infants with FIP. Our primary objective was to evaluate the antimicrobial use in VLBW infants with FIP in a cohort of the German Neonatal Network (GNN). The secondary objective was to characterize a subset in detail as a benchmark for future targets of stewardship. METHODS: Data on VLBW infants with FIP was collected prospectively within the GNN, a collaboration of 68 neonatal intensive care units (NICU). With regards to the primary objective, patient characteristics and antimicrobial treatment were extracted from the predefined GNN database. To address our secondary objective, an additional on-site assessment of laboratory and microbiological culture results were performed. RESULTS: In the GNN cohort, 613/21,646 enrolled infants (2.8%) developed FIP requiring surgery. They were frequently treated with carbapenems (500/613 (81.6%)) and vancomycin (497/613 (81.1%)). In a subset of 124 VLBW infants, 77 (72.6%) had proof of gram-positive bacteria in the abdominal cavity, coagulase-negative staphylococci (CoNS) predominantly. Despite the low prevalence of gram-negative bacteria (n = 6 (4.8%)), the combination of meropenem and vancomycin was prescribed most frequently (n = 96 (78.0%)). CONCLUSION: The use of carbapenems as broad-spectrum antimicrobials agents might not be justified in most VLBW infants with FIP. Knowledge on the development of the neonatal gut microbiota, local resistance patterns and individual microbiological findings should be taken into consideration when implementing antimicrobial stewardship programs (ASPs).

Comprehensive analysis of antimicrobial resistance in the Southwest Indian Ocean: focus on WHO critical and high priority pathogens.

The spread of antimicrobial resistance (AMR) is a major global concern, and the islands of the Southwest Indian Ocean (SWIO) are not exempt from this phenomenon. As strategic crossroads between Southern Africa and the Indian subcontinent, these islands are constantly threatened by the importation of multidrug-resistant bacteria from these regions. In this systematic review, our aim was to assess the epidemiological situation of AMR in humans in the SWIO islands, focusing on bacterial species listed as priority by the World Health Organization. Specifically, we examined Enterobacterales, Acinetobacter spp., Pseudomonas spp. resistant to carbapenems, and Enterococcus spp. resistant to vancomycin. Our main objectives were to map the distribution of these resistant bacteria in the SWIO islands and identify the genes involved in their resistance mechanisms. We conducted literature review focusing on Comoros, Madagascar, Maldives, Mauritius, Mayotte, Reunion Island, Seychelles, Sri Lanka, and Zanzibar. Our findings revealed a growing interest in the investigation of these pathogens and provided evidence of their active circulation in many of the territories investigated. However, we also identified disparities in terms of data availability between the targeted bacteria and among the different territories, emphasizing the need to strengthen collaborative efforts to establish an efficient regional surveillance network.